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https://www.readbyqxmd.com/read/28107776/activity-based-probes-for-the-multicatalytic-proteasome
#1
REVIEW
David S Hewings, John A Flygare, Ingrid E Wertz, Matthew Bogyo
Proteasomes are multisubunit protease complexes responsible for degrading most intracellular proteins. In addition to removing damaged proteins, they regulate many important cellular processes through the controlled degradation of transcription factors, cell cycle regulators and enzymes. Eukaryotic proteasomes have three catalytic subunits, β1, β2 and β5, that each have different substrate specificities. Additionally, although we know that diverse cell types express proteasome variants with distinct activity and specificity profiles, the functions of these different pools of proteasomes are not fully understood...
January 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28107627/use-of-tissue-metabolite-analysis-and-enzyme-kinetics-to-discriminate-between-alternate-pathways-for-hydrogen-sulfide-metabolism
#2
Kristie D Cox Augustyn, Michael R Jackson, Marilyn Schuman Jorns
Hydrogen sulfide (H2S) is an endogenously synthesized signaling molecule that is enzymatically metabolized in mitochondria. The metabolism of H2S maintains optimal concentrations of the gasotransmitter and produces sulfane sulfur (S(0))-containing metabolites that may be functionally important in signaling. Sulfide:quinone oxidoreductase (SQOR) catalyzes the initial 2-electron oxidation of H2S to S(0) using coenzyme Q as electron acceptor in a reaction that requires a third substrate to act as the acceptor of S(0)...
January 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28107625/gold-nanoshell-mediated-remote-myotube-activation
#3
Attilio Marino, Satoshi Arai, Yanyan Hou, Andrea Degl'Innocenti, Valentina Cappello, Barbara Mazzolai, Young-Tae Chang, Virgilio Mattoli, Madoka Suzuki, Gianni Ciofani
Mild heat stimulation of muscle cells within the physiological range represents an intriguing approach for the modulation of their functions. In this work, photothermal conversion was exploited to remotely stimulate striated muscle cells by using gold nanoshells (NS) in combination with near-infrared (NIR) radiation. Temperature increments of approximately 5°C were recorded by using an intracellular fluorescent molecular thermometer and were demonstrated to efficiently induce myotube contraction. The mechanism at the base of this phenomenon was thoroughly investigated and was observed to be a Ca2+-independent event directly involving actin-myosin interactions...
January 20, 2017: ACS Nano
https://www.readbyqxmd.com/read/28107550/enhanced-trpc-channel-mediated-ca-2-influx-in-the-cells-with-phospholipase-c-%C3%AE-1-overexpression-its-possible-role-in-coronary-artery-spasm
#4
Kazuo Murakami, Tomohiro Osanai, Makoto Tanaka, Kimitaka Nishizaki, Takahiko Kinjo, Tomohiro Tanno, Yuji Ishida, Akiko Suzuki, Tomohide Endo, Hirofumi Tomita, Ken Okumura
We reported that coronary spasm was induced in the transgenic mice with the increased phospholipase C (PLC)-δ1 activity. We investigated the effect of enhanced PLC-δ1 on Ca(2+) influx and its underlying mechanisms. We used human embryonic kidney (HEK)-293 and coronary arteries-smooth-muscle cells (CASMC). Intracellular free Ca(2+) concentration ([Ca(2+) ]i ) (nM) was measured by fura-2, and Ca(2+) influx was evaluated by the increase in [Ca(2+) ]i after addition of extracellular Ca(2+) . Acetylcholine (ACh) was used to induce Ca(2+) influx...
January 20, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28107503/osteopontin-affects-insulin-vesicle-localization-and-ca2-homeostasis-in-pancreatic-beta-cells-from-female-mice
#5
Anna Wendt, Inês G Mollet, Anki Knutsson, Victor S Bolmgren, Anna Hultgårdh-Nilsson, Maria F Gomez, Lena Eliasson
Type 2 diabetic patients suffer from insulin resistance and reduced insulin secretion. Osteopontin (OPN), a versatile protein expressed in several tissues throughout the body including the islets of Langerhans, has previously been implicated in the development of insulin resistance. Here we have investigated the role of OPN in insulin secretion using an OPN knock out mouse model (OPN-/-). Ultra-structural analyzes of islets from OPN-/- and WT mice indicated weaker cell-cell connections between the islet cells in the OPN-/- mouse compared to WT...
2017: PloS One
https://www.readbyqxmd.com/read/28107450/systemic-t-cells-immunosuppression-of-glioma-stem-cell-derived-exosomes-is-mediated-by-monocytic-myeloid-derived-suppressor-cells
#6
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, Federica Caponnetto, Ivana Manini, Antonio Paolo Beltrami, Tamara Ius, Miran Skrap, Carla Di Loreto, Giorgia Gri
A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes...
2017: PloS One
https://www.readbyqxmd.com/read/28107406/classification-and-segmentation-of-nanoparticle-diffusion-trajectories-in-cellular-micro-environments
#7
Thorsten Wagner, Alexandra Kroll, Chandrashekara R Haramagatti, Hans-Gerd Lipinski, Martin Wiemann
Darkfield and confocal laser scanning microscopy both allow for a simultaneous observation of live cells and single nanoparticles. Accordingly, a characterization of nanoparticle uptake and intracellular mobility appears possible within living cells. Single particle tracking allows to measure the size of a diffusing particle close to a cell. However, within the more complex system of a cell's cytoplasm normal, confined or anomalous diffusion together with directed motion may occur. In this work we present a method to automatically classify and segment single trajectories into their respective motion types...
2017: PloS One
https://www.readbyqxmd.com/read/28107238/roles-of-the-endoplasmic-reticulum-stress-transducer-oasis-in-ossification-of-the-posterior-longitudinal-ligament
#8
Yu Chen, Haisong Yang, Jinhao Miao, Xiaowei Liu, Xinwei Wang, Deyu Chen
STUDY DESIGN: In vitro molecular research on the posterior longitudinal ligament fibroblasts. OBJECTIVE: To investigate different expression of old astrocyte specifically induced substance (OASIS) between spinal ligament fibroblasts from the patients with ossification of the posterior longitudinal ligament (OPLL) and from non-OPLL patients and demonstrate knockdown of OASIS protein expression by RNA interference inhibiting expression of type I collagen (COL I) in OPLL cells...
February 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28107195/a-new-hdac-inhibitor-cinnamoylphenazine-shows-antitumor-activity-in-association-with-intensive-macropinocytosis
#9
Bing-Yan Zhu, Bo-Yang Shang, Yue Du, Yi Li, Liang Li, Xian-Dong Xu, Yong-Su Zhen
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107086/interaction-between-lipid-droplets-and-endoplasmic-reticulum-in-human-atherosclerotic-plaques
#10
Ida Perrotta
Lipid droplets (LDs) are intracellular organelles that are found in nearly all cell types, where they serve fundamental roles in lipid metabolism and energy homeostasis. Traditionally considered as simple lipid storage deposits, these dynamic and remarkable organelles have recently been implicated in a number of other cellular functions, ranging from protein storage and degradation to virus replication. Intracellular accumulation of LDs is also a hallmark feature of diverse human diseases including diabetes type II, obesity, hepatosteatosis, cancer, and atherosclerosis...
January 20, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28107023/doxorubicin-delivery-into-tumor-cells-by-stable-cavitation-without-contrast-agents
#11
Kamel Chettab, Jean-Louis Mestas, Maxime Lafond, Djamel Eddine Saadna, Cyril Lafon, Charles Dumontet
Doxorubicin, alone or in combination with other anticancer agents, is one of the most widely used chemotherapeutic agents and is administered in a wide range of cancers. However, the use of doxorubicin is limited due to its potential serious adverse reactions. Previous studies have established the ability of high intensity focused ultrasound (HIFU) in combination with various contrast agents to increase intracellular doxorubicin delivery in a targeted and noninvasive manner. In this study, we developed a new sonoporation device generating and monitoring acoustic cavitation bubbles without any addition of contrast agents...
January 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#12
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28106847/combination-of-morroniside-and-diosgenin-prevents-high-glucose-induced-cardiomyocytes-apoptosis
#13
Wen-Xia Pi, Xiao-Peng Feng, Li-Hong Ye, Bao-Chang Cai
Cornus officinalis and Dioscorea opposita are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic cardiomyopathy. Morroniside (Mor) of Cornus officinalis and diosgenin (Dio) of Dioscorea opposita formed an innovative formula named M + D. The aims of the present study were to investigate myocardial protective effect of M + D on diabetic cardiomyopathy (DCM) through the inhibition of expression levels of caspase-3 protein, and identify the advantage of M + D compared with Mor, Dio, and the positive drug metformin (Met)...
January 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106805/synthetic-assembly-of-mannose-moieties-using-polymer-chemistry-and-the-biological-evaluation-of-its-interaction-towards-concanavalin-a
#14
Deepti Diwan, Kohei Shinkai, Toshihiro Tetsuka, Bin Cao, Hidenao Arai, Tetsuo Koyama, Ken Hatano, Koji Matsuoka
Protein-carbohydrate interactions exhibit myriad intracellular recognition events, so understanding and investigating their specific interaction with high selectivity and strength are of crucial importance. In order to examine the effect of multivalent binding on the specificity of protein-carbohydrate interactions, we synthesized mannose glycosides as a novel type of glycosylated monomer and glycopolymers of polyacrylamide derivatives with α-mannose (α-Man) by radical polymerization and monitored their strength of interaction with concanavalin A (Con A) by surface plasmon resonance (SPR) detection...
January 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#15
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106772/neuroprotective-and-anti-apoptotic-effects-of-csp-1103-in-primary-cortical-neurons-exposed-to-oxygen-and-glucose-deprivation
#16
Vanessa Porrini, Ilenia Sarnico, Marina Benarese, Caterina Branca, Mariana Mota, Annamaria Lanzillotta, Arianna Bellucci, Edoardo Parrella, Lara Faggi, Pierfranco Spano, Bruno Pietro Imbimbo, Marina Pizzi
CSP-1103 (formerly CHF5074) has been shown to reverse memory impairment and reduce amyloid plaque as well as inflammatory microglia activation in preclinical models of Alzheimer's disease. Moreover, it was found to improve cognition and reduce brain inflammation in patients with mild cognitive impairment. Recent evidence suggests that CSP-1103 acts through a single molecular target, the amyloid precursor protein intracellular domain (AICD), a transcriptional regulator implicated in inflammation and apoptosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106756/inhibitory-effects-of-constituents-from-the-aerial-parts-of-rosmarinus-officinalis-l-on-triglyceride-accumulation
#17
Jian Li, Tiwalade Adegoke Adelakun, Sijian Wang, Jingya Ruan, Shengcai Yang, Xiaoxia Li, Yi Zhang, Tao Wang
Sixteen flavonoids (1-16) including two new ones, named officinoflavonosides A (1) and B (2) were obtained from the aerial parts of Rosmarinus officinalis. Among the known ones, 6, 10, and 13 were isolated from the rosmarinus genus for the first time. Their structures were elucidated by chemical and spectroscopic methods. Moreover, the effects on sodium oleate-induced triglyceride accumulation (TG) in HepG2 cells of the above-mentioned compounds and 16 other isolates (17-32) reported previously to have been obtained in the plant were analyzed...
January 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28106541/cell-membrane-and-intracellular-expression-of-toll-like-receptor-9-tlr9-in-colorectal-cancer-and-breast-cancer-cell-lines
#18
Shadab Shahriari, Somayeh Rezaeifard, Hamid Reza Moghimi, Mohammad Reza Khorramizadeh, Zahra Faghih
BACKGROUND: Toll-like receptor 9 (TLR9) is a DNA receptor of innate immune system which plays a pivotal role in inflammatory response. Recent evidence reveals over-expression and functionality of TLR9 in a wide variety of cancer cells and its contribution to tumor cell proliferation and survival. OBJECTIVE: In this study, we assessed the aberrant cell surface expression of TLR9 in cancer using cell-lines model. METHODS: Three breast cancer cell-lines (MDA-MB-231, MCF7 and SKBR3) and five colorectal adenocarcinoma cell-lines (HT29, HT29/219, SW480, SW48 and SW1116) in addition to one primary foreskin isolated fibroblast cell were analyzed for cell surface and intracellular expression of TLR9 by flow cytometry method...
January 13, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28106386/macromolecularly-caged-carbon-nanoparticles-for-intracel-lular-trafficking-via-switchable-photo-luminescence
#19
Santosh K Misra, Indrajit Srivastava, Indu Tripathi, Enrique A Daza, Fatemeh Ostadhossein, Dipanjan Pan
Reversible switching of photoluminescence (PL) of carbon nanoparticles (CNP) can be achieved with counter-ionic macromolecular caging and de-caging at the nanoscale. A negatively charged uncoated, 'bare' CNP with high luminescence loses its PL when positively charged macromolecules are wrapped around its surface. Prepared caged carbons could regain their emission only through interaction with anionic surfactant mole-cules, representing anionic amphiphiles of endocytic membranes. This process could be verified by gel electrophoresis, spectroscopically and in vitro confocal imaging studies...
January 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28106292/23-hydroxytormentic-acid-protects-human-dermal-fibroblasts-by-attenuating-uva-induced-oxidative-stress
#20
Hae Jeong Youn, Ki Bbeum Kim, Hyo-Sun Han, In-Sook An, Kyu Joong Ahn
Ultraviolet A (UVA), one of the major components of sunlight, can penetrate the dermal layer of the skin and generate reactive oxygen species (ROS). It causes alterations in the dermal connective tissue and gene expression, inflammation, photoaging, and DNA damage. Therefore, the harmful effects of UVA and strategies to reduce it have been consistently investigated. 23-Hydroxytormentic acid (23-HTA) has been demonstrated to improve drug-induced nephrotoxicity and exhibit several free radical scavenging effects with other molecules...
January 20, 2017: Photodermatology, Photoimmunology & Photomedicine
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